失眠症是一种临床常见的难治性疾病，与褪黑素分泌减少相关。失眠症是针灸治疗的优势病种。前期研究表明，耳甲区有迷走神经分布，耳甲区电刺激（经皮迷走神经刺激，Transcutaneous vagus nerve stimulation，ta-VNS ）能够促进褪黑素分泌，引起大鼠血浆褪黑素水平显著增加，上调褪黑素一型受体MT1的表达。本课题通过动物实验研究进一步阐明ta-VNS对失眠模型大鼠褪黑素能系统的调节效应，包括褪黑素分泌和对MT1表达的调节作用；通过临床随机对照试验明确ta-VNS治疗失眠症的疗效；通过脑功能磁共振研究探索ta-VNS治疗失眠症的中枢效应机制，证实我们的假说：耳甲区电针通过体表迷走神经刺激调制边缘叶-觉醒脑功能网络（特别是松果体、下丘脑、孤束核及杏仁核等结构）调节褪黑素能系统调整睡眠，为临床应用ta-VNS治疗失眠症提供有力的科学依据。

Insomnia is a common and clinically refractory disease but testified as a disorder that can be treated with acupuncture. Insomnia is related to a decreased secretion of melatonin and a down regulated expression of melatonin receptor type 1 (MT1) in the central nervous system. Our preliminary results show that there are vagal innervations in the auricular concha area and transcutaneous vagus nerve stimulation (ta-VNS) which can promote the melatonergic system, as demonstrated by the facts that ta-VNS acutely elevated the concentration of melatonin in rats, and significantly up-regulated the expression of melatonin receptor type 1 (MT1). In this application we would further 1) explore the involvement of the promoted /restored melatonergic system in the mechanism of the therapeutic effectiveness of ta-VNS on insomnia in experimental animal model of insomnia, and 2) verify the therapeutic effectiveness of ta-VNS in clinical insomnia patients. The project would be able 1) to clarity the promoting effect of ta-VNS on the melatonergic system in rodent insomnia model, including the secretion amount, rhythm, sources of melatonin and its up-regulating effect on the MT1 expression; and 2) to evaluate the effectiveness of ta-VNS on the quantity and rhythm of melatonin secretion, and its therapeutic effect in insomnia patients. The outcome from this project will help us to understand the mechanism of the acupuncture effectiveness and to provide scientific evidence of the therapeutic effectiveness of ta-VNS on insomnia and other diseases with low circulating melatonin level implicated.